{
    "title": "DDD107498 vs Malaria",
    "inventor_name": "Ian Gilbert",
    "publication_year": 2015,
    "device_name": "DDD107498",
    "goal": "Treat malaria with a single dose, prevent disease spread, and provide prophylactic protection.",
    "problem_addressed": "Malaria infection and drug-resistant Plasmodium parasites.",
    "concept_summary": "DDD107498 is a novel quinoline-4-carboxamide compound that inhibits the protein-synthesis machinery of Plasmodium parasites across all life-cycle stages, enabling a single-dose oral therapy that clears blood and liver infections and blocks transmission.",
    "detailed_description": "The compound was discovered by the Drug Discovery Unit at the University of Dundee in collaboration with Medicines for Malaria Venture. In mouse and other animal studies the drug cleared parasites from both blood and liver, targeting a protein involved in the production of vital enzymes within the parasite. It acts on multiple life stages, including gametocytes, giving it transmission-blocking potential. The invention also covers processes for synthesising the quinoline-4-carboxamide core and related intermediates. Results have been published in Nature and first-in-human clinical trials are planned.",
    "principles": [
        "Inhibition of parasite protein synthesis",
        "Targeting a conserved protein involved in enzyme production",
        "Single-dose pharmacokinetics"
    ],
    "scientific_domains": [
        "Pharmacology",
        "Medicinal Chemistry",
        "Parasitology"
    ],
    "mechanisms_of_action": [
        "Binds to a protein essential for parasite protein production",
        "Disrupts enzyme synthesis across blood, liver and gametocyte stages"
    ],
    "materials": [
        "Quinoline-4-carboxamide compound (DDD107498)",
        "Synthetic intermediates for quinoline-4-carboxamide"
    ],
    "energy_sources": [],
    "inputs": [
        "Oral administration (single dose)",
        "Standard formulation excipients"
    ],
    "outputs": [
        "Clearance of Plasmodium from blood",
        "Clearance of Plasmodium from liver",
        "Reduced transmission potential"
    ],
    "claimed_performance": "Single-dose cure of malaria, effective against drug-resistant strains, blocks transmission, and can be produced for <$1 per dose.",
    "experimental_evidence": "Mouse and other lab-animal tests showed complete parasite clearance from blood and liver; results published in Nature; first phase clinical trials announced.",
    "replication_status": "Results published in Nature; pre-clinical animal data available; human trials pending.",
    "keywords": [
        "malaria",
        "antimalarial",
        "single dose",
        "quinoline-4-carboxamide",
        "protein synthesis inhibitor",
        "drug resistance"
    ],
    "related_technologies": [
        "Artemisinin-based combination therapies",
        "Other quinoline antimalarials"
    ],
    "controversy_level": "low",
    "confidence_score": 0.9,
    "practicability_score": 0.8,
    "fringe_score": 0.1,
    "evidence_strength": 0.7,
    "risk_score": 0.2,
    "trl_estimate": 6,
    "source_urls": [
        "http://www.sciencealert.com/new-drug-has-the-potential-to-ward-off-malaria-with-a-single-dose",
        "http://www.dundee.ac.uk/news/2015/discovery-of-a-novel-antimalarial-compound-published-in-nature.php",
        "https://www.youtube.com/watch?v=I2qHc4YTDSg"
    ],
    "organizations": [
        "University of Dundee - Drug Discovery Unit",
        "Medicines for Malaria Venture"
    ],
    "applications": [
        "Treatment of acute malaria infection",
        "Prophylactic protection against malaria",
        "Transmission-blocking in endemic regions"
    ],
    "limitations": [
        "Only pre-clinical data available; human safety not yet demonstrated",
        "Manufacturing scale-up and regulatory approval pending"
    ],
    "open_questions": [
        "What is the safety profile in humans?",
        "Will resistance develop against the protein-synthesis target?",
        "Can the formulation be stable and affordable at scale?"
    ],
    "red_flags": [],
    "evidence_quotes": [
        "Lab tests have highlighted the potential of a new drug to treat malaria in affected patients, prevent it from spreading, and ward off future infections with a single dose.",
        "In tests with mice and other lab animals, the researchers report that the drug identified and attacked the protein involved in the production of various vital enzymes and proteins in the malaria parasite's cells throughout all stages of its lifecycle, which prevented the spread and development of the disease.",
        "The parasite was successfully cleared from both the blood and livers of the affected animals.",
        "The compound we have discovered works in a different way to all other antimalarial medicines on the market or in clinical development, which mean that it has great potential to work against current drug-resistant parasites.",
        "The results have been published in Nature."
    ],
    "category": "Chemistry & Chemical Processes"
}